This year the Genetics Services Research Unit of SBRB conducted and analyzed data from a randomized controlled study of two consent interventions to genome sequencing studies; conducted studies on baseline data from the ClinSeq cohort and collaborated on studies of women diagnosed with breast cancer at a young age and caretakers of boys with Duchenne and Becker muscular dystrophies, as examples. 1. RCT of consent interventions: Decisions to participate in genome sequencing studies that return results present challenges to achieving informed choice due to the scope and uncertainty of the information potentially generated. Increasingly studies include return of secondary findings that participants need to understand. This study compared an evidence-based novel consent to a standard consent among 212 women affected with primary ovarian insufficiency and eligible to participate in a sequencing study. Equivalence was assumed in the study design to assess whether knowledge and decision to participate differed between the two consent groups and whether any harms were introduced by the novel consent. No difference was found between the arms in knowledge and decision to participate. There were differences in informed choice about learning secondary variants with 96 (45%) making informed choices and 92 (43%) making less informed choices, with more of the second group coming from the novel consent group. Results suggest that decisions to learn secondary variants may be more challenging for participants and depend on how sufficient knowledge for an informed choice is defined. Although the novel consent was as effective in facilitating decisions to participate in a genome sequencing study, it was less effective, and thus not equivalent, in achieving informed choice to receive secondary variant results. Questions raised by participants suggest differences between primary and secondary variants should be emphasized. 2. Responses to and communication of findings among ClinSeq participants: This study investigated how genome sequencing results affect health behaviors, affect, and communication. We report on 29 participants who received a sequence result in the ClinSeq study, a cohort of well-educated, postreproductive volunteers. A mixed-methods design was used to explore respondents' use, communication, and perceived utility of results. Most participants (72%) shared their result with at least one health-care provider, and 31% reported subsequent changes in the health care they received. Participants scored high on the Positive Experiences subscale and low on the Distress subscale of a modified version of the Multidimensional Impact of Cancer Risk Assessment. The majority (93%) shared their result with at least one family member. Participants described deriving personal utility from their results. This article is the first to describe research participants' reactions to actionable sequencing results. Our findings suggest clinical and personal benefit from receiving sequencing results, both of which may contribute to improved health for the recipients. Given the participants' largely positive or neutral affective responses and disclosure of their results to physicians and relatives, health-care providers should redirect concern from the potential for distress and attend to motivating patients to follow their medical recommendations. 3. Perceived ambiguity as a barrier to intentions to learn results from genome sequencing: Many variants that could be returned from genome sequencing may be perceived as ambiguous-lacking reliability, credibility, or adequacy. Little is known about how perceived ambiguity influences thoughts about sequencing results. Participants (n = 494) in an NIH genome sequencing study completed a baseline survey before sequencing results were available. We examined how perceived ambiguity regarding sequencing results and individual differences in medical ambiguity aversion and tolerance for uncertainty were associated with cognitions and intentions concerning sequencing results. Perceiving sequencing results as more ambiguous was associated with less favorable cognitions about results and lower intentions to learn and share results. Among participants low in tolerance for uncertainty or optimism, greater perceived ambiguity was associated with lower intentions to learn results for non-medically actionable diseases; medical ambiguity aversion did not moderate any associations. Results are consistent with the phenomenon of ambiguity aversion and may influence whether people learn and communicate genomic information. 4. Decision making for Duchenne muscular dystrophy trials: This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit-risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. The majority of parents described undertaking benefit-risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm.